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Functional analysis of acetylcholine receptor using muscarinic receptor knockout mice.

使用毒蕈碱受体敲除小鼠对乙酰胆碱受体进行功能分析。

基本信息

批准号：
18390073
负责人：
FUJII Takeshi
金额：
$ 10.77万
依托单位：
Doshisha Women's College of Liberal Arts (2007)The University of Tokyo (2006)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

Muscarinic acetylcholine receptor (mAChR) knockout (KO) mice, which were developed and supplied by Dr Matsui (Chiba Institute of Science), were used. Regulation of Immunological response: On the 14th day after immunization, serum antigen specific IgG_1 levels in M_1/M5-KO mice were significantly lower than those of wild-type mice. In addition, concanavalin A-induced ChAT, an ACh-synthesizing enzyme, interleukin-2 and c-fos mRNA expression in wild-type mice. These gene expressions were significantly reduced, in M_3 KO-mice, when compared with those of wild-type mice. These findings suggested that M_1/M_5 and M_3 mAChR may involved in regulation of lymphocyte function. Relaxation of Urinary bladder muscle: In wild-type mice, carbachol (CCh) relaxed noradrenaline-induced contraction in a dose-dependent manner. However, relaxation by CCh was decreased in M_3-KO mice, but not changed in M_2-KO mice. In addition, CCh-induced response was antagonized by indomethacin. In addition, PGE_2 induce … More d concentration dependent relaxation. These findings suggest that M_3 mAChR and PGE_2 are involved in relaxation of urinary bladder muscle. Changes in mAChR ligand properties: Characterization of mAChR binding activity in the bladder and submandibular gland after oral administration of oxybutynin (Oxy) and solifenacin (Sol) to M_2-KO mice was performed. There was little difference between bladder and submandibular gland of M_2-KO mice in in vitro mAChR binding activities of Oxy and Sol, suggesting equal affinity to the residual (predominantly M_3) mAChR in both tissues. In contrast, compared with that after oral Oxy, oral Sol exerted significantly greater binding activity to the bladder mAChR of M_2-KO mice, whereas oral Sol exhibited significantly smaller binding activity to the exocrine gland mAChR. These data indicate that oral Sol, unlikely oral, may exert greater binding to M_3 mAChR of bladder than exocrine gland under in vivo condition. Oral Sol may be advantageous for the treatment of overactive bladder, in terms of high selectivity to bladder. Less

使用由Dr Matsui（千叶科学研究所）开发和提供的毒蕈碱乙酰胆碱受体（mAChR）敲除（KO）小鼠。免疫应答的调节：免疫后第14天，M_1/M5-KO小鼠血清抗原特异性IgG_1水平明显低于野生型小鼠。此外，伴刀豆球蛋白A诱导ChAT，乙酰胆碱合成酶，白细胞介素2和c-fos mRNA表达在野生型小鼠。与野生型小鼠相比，M_3 KO小鼠中这些基因的表达显著降低。提示M_1/M_5和M_3mAChR可能参与淋巴细胞功能的调节。膀胱肌的松弛：在野生型小鼠中，卡巴胆碱（CCh）以剂量依赖性方式松弛去甲肾上腺素诱导的收缩。而M_2-KO小鼠则无明显变化。此外，消炎痛可拮抗Cch诱导的反应。此外，PGE_2还可诱导 ...更多信息 d浓度依赖性弛豫。提示M_3mAChR和PGE_2参与了膀胱肌的舒张作用。mAChR配体性质的变化：对口服奥昔布宁（Oxy）和索利那新（Sol）后的M_2-KO小鼠进行膀胱和下颌下腺中mAChR结合活性的表征。Oxy和Sol对M_2-KO小鼠膀胱和下颌下腺中mAChR的体外结合活性无明显差异，表明两者对残留（主要是M_3）mAChR的亲和力相等。与口服Oxy相比，口服Sol对M_2-KO小鼠膀胱mAChR的结合活性显著增强，而对外分泌腺mAChR的结合活性显著减弱。这些结果表明，在体内条件下，口服Sol可能比口服Sol更能与膀胱M_3 mAChR结合。就对膀胱的高选择性而言，口服溶胶可能有利于治疗膀胱过度活动症。少

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Characterization of muscarinic receptor(mR) binding oral administration of anticholinergic agents in muscarinic M_2 knockout mice.

毒蕈碱受体 (mR) 结合口服抗胆碱能药物在毒蕈碱 M_2 敲除小鼠中的表征。

DOI：
发表时间：
2007
期刊：
影响因子：
0
作者：
Tsukiyama;T.;et. al;Luvasandorj O
通讯作者：
Luvasandorj O

Involvement of M_2 muscarinic receptors in relaxant response of circular muscle of mouse gastric antrum.

M_2毒蕈碱受体参与小鼠胃窦环肌松弛反应。

DOI：
发表时间：
2006
期刊：
Neurogastroenterol. Motil 18
影响因子：
0
作者：
Hiramatsu;Y.;Kitagawa;K.;Suzuki;T.;Uchida;C.;Hattori;T.;Kikuchi;H.;Oda;T.;Hatakevama S.;Nakayama;K-i.;Yamamoto;T.;Konno;H. and Kitagawa;M.;Takeuchi T
通讯作者：
Takeuchi T

M_2 and M_3 muscarinic receptors are involved in enteric nerve-mediated contraction of the mouse ileum:findings obtained using muscarinic receptor knockout mouse

M_2和M_3毒蕈碱受体参与肠神经介导的小鼠回肠收缩：使用毒蕈碱受体敲除小鼠获得的发现